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New Approaches to Synthetic Lethality for Mutant KRAS-Dependent Cancer

The structure of the KRAS protein is visible in this artistic rendering.
Credit: National Cancer Institute

The New Approaches to Synthetic Lethality for Mutant KRAS-Dependent Cancer Network from 2015 - 2021 (funded through PAR-14-314) was a collaborative effort of DCB with NCI’s Office of the Director and Division of Cancer Treatment and Diagnosis (DCTD). The projects used next-generation approaches and model systems to identify new targets whose inhibition would induce synthetic lethality in cancers dependent on the expression of mutant KRAS.

Investigators supported by this initiative formed a collaborative network that encouraged the exchange of results and resources, participation in cross-validation of potential targets, and interacted regularly with the RAS Initiative team at the Frederick National Laboratory for Cancer Research (FNLCR).

About the Network

In 2014, NCI held the Synthetic Lethality Screens for Finding KRAS Vulnerabilities Workshop, which focused on new technologies (e.g., 3D cell culture, and in vivo systems) to identify strategies for targeting mutant KRAS. Discussions from this meeting led to the formation of the Synthetic Lethality for Mutant KRAS-Dependent Cancer Network.

Additional information about the teams and research projects that were supported through the program can be found at the RAS Initiative.

Past Projects

Institution Principal Investigator(s) Project Title
Broad Institute William Hahn Systematic identification of oncogenic KRAS synthetic lethal interactions
Dana-Farber Cancer Center Kevin Haigis, Stephen Elledge A multi-faceted approach to identifying K-Ras synthetic lethal relationships
Memorial Sloan Kettering Cancer Center Charles Rudin Identification and validation of synthetic lethality in KRAS mutant lung adenocarcinoma patient derived xenografts
Stanford University Peter Jackson, Michael Bassik, Eric Sweet-Cordero Using protein interaction networks and combinatorial Screens to target KRAS driven cancer
Stanford University Calvin Kuo, Kevin Shokat Modeling KRAS-dependent synthetic lethality in human colon organoids
University of North Carolina Chapel Hill Channing Der, Adrienne Cox Identification of synthetic lethal interactors in pancreatic cancer
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